Despite evidence that +/-3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy&am... more Despite evidence that +/-3,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') causes persistent alterations to the serotonergic system of animals, evidence for long-term neurological effects of ecstasy/MDMA in humans remains equivocal. The current study assessed serotonin functioning of nine male and 11 female recreational ecstasy polydrug users by measuring neuroendocrine (prolactin, cortisol) responses to pharmacological challenge with the selective serotonin reuptake inhibitor citalopram, compared with nine male and five female cannabis polydrug users and 11 male and 11 female non-drug using controls. A single-blind, randomised, placebo-controlled design was used. Subjective responses, other substance use, mood, personality traits and demographic variables were measured to control for potentially confounding variables. There were no significant differences between ecstasy polydrug users, cannabis polydrug users and non-drug using controls in neuroendocrine or subjective responses to serotonergic challenge, and there were no sex by drug group interactions. There was no relationship between extent of ecstasy use and neuroendocrine functioning, alone or in combination with potential confounding variables. Subjective responses to the pharmacological challenge (nausea, tremor, dry mouth), novelty seeking and lifetime dose of alcohol were the only variables that contributed to one or more of the neuroendocrine outcome variables. These data do not support the premise that recreational ecstasy/MDMA use results in measurable impairment of serotonergic control of endocrine activity.
The two fundamental parameters of corticotropin (ACTH) secretion are the number of secreting cort... more The two fundamental parameters of corticotropin (ACTH) secretion are the number of secreting corticotropes and the amount of ACTH secreted by each cell. We have measured these parameters in rat corticotropes in response to increasing concentrations of corticotropin-releasing factor (CRF) or arginine vasopressin (AVP). Increasing concentrations of AVP stimulated more corticotropes to secrete, while the amount of ACTH each cell secreted remained relatively fixed (nongraded secretory response). Conversely, increasing concentrations of CRF stimulated more ACTH secretion per cell (graded secretory response), while the number of secretory cells remained relatively constant. When viewed from the perspective of a single corticotrope, it was clear that CRF and AVP induced completely distinct specific responses. We have previously shown, and provide further evidence here, that secretory responses to CRF or AVP occur in the same cell. It is therefore apparent that a single corticotrope is able to generate either a graded, or a nongraded secretory response. We have also considered the potential intracellular changes that must direct graded or nongraded secretion. It is generally accepted that CRF stimulates activation of adenylate cyclase, whereas AVP activates phosphoinositidase in pituitary corticotropes. Our findings, and others surveyed here, suggest that the activation of adenylate cyclase results in graded secretion, while the activation of phosphoinositidase induces the nongraded secretion. Graded or nongraded secretion may therefore be linked to specific second messengers. It is hypothesized that the inositol 1,4,S-trisphosphate-mediated release of an intracellular Ca2+ store constitutes a mechanism whereby phosphoinositidase-coupled hormones set in motion the nongraded secretory response. These findings suggest novel functions for individual second messengers.
Local communication among cells of the anterior pituitary appears to play an important role in th... more Local communication among cells of the anterior pituitary appears to play an important role in the regulation of ACTH secretion. Dissociated pituitary cells were plated as a monolayer at decreasing concentrations of cells (increasing the distance between cells and, thus, decreasing their potential interactions), and ACTH secretion was measured from individual corticotropes using a specific reverse hemolytic plaque assay. There was a critical intercell distance above which significant changes in the number of CRF-responsive corticotropes were observed. Provided that this critical distance was not exceeded the number of secretory corticotropes in response to CRF (10 nM) was relatively constant, thereby defining a fraction of corticotropes that was robustly CRF responsive. In contrast, when this critical distance between cells was exceeded, the number of CRF-responsive corticotropes progressively increased to almost double their original number, thereby defining a second fraction of CRF-responsive corticotropes that was previously repressed. These observations suggest the presence of a paracrine factor that profoundly inhibits CRF-stimulated ACTH secretion from a repressed fraction of corticotropes. Further independent studies confirmed and extended these observations. We identified the cellular source of the inhibitory factor as the robustly CRF-responsive fraction of corticotropes. Pituitary cells were identified by reverse hemolytic plaque assay and then destroyed using a laser photoablation procedure that did not compromise the remaining cells. The pituitary cells were separated by a distance at which the inhibitory factor was fully effective. Destruction of the cellular source of the paracrine inhibition would, therefore, allow secretion from the previously repressed fraction of corticotropes. Accordingly, when robustly CRF-responsive corticotropes were destroyed, a significant number of previously repressed corticotropes appeared in a second assay. Destruction of somatotropes or a cell adjacent to a robustly CRF-responsive corticotrope did not alter the number of CRF-stimulated corticotropes among the remaining cells. We conclude that a paracrine factor liberated by the robustly CRF-responsive corticotropes inhibits ACTH secretion from the repressed fraction of corticotropes. The robustly CRF-responsive corticotropes appear unresponsive to the effects of the factor, and the repressed corticotropes are unlikely to secrete it. A role of this paracrine communication is to hold corticotropes in reserve and, therefore, prevent the severe depletion of hormone. This form of paracrine communication may be a specialized adaption among cells where the physiological setting demands robust secretory responses to multiple stimuli. The experimental paradigms developed here may be extremely useful for 1) screening potential paracrine factors and 2) determining whether the secretion of the paracrine factor is regulated by adrenal or hypothalamic hormones.
An assessment framework provides a structured conceptual map of the learning outcomes of a progra... more An assessment framework provides a structured conceptual map of the learning outcomes of a programme of study along with details of how achievement of the outcomes can be measured. The rationale for using frameworks to underpin the targeting of essential content components is especially relevant for the medical education community. Frameworks have the capacity to improve validity and reliability in assessment, allowing test developers to more easily create robust assessment instruments. The framework used by the Australian Medical Assessment Collaboration (AMAC) is an interesting and relevant case study for the international community as it draws and builds on established processes in higher education assessment. The AMAC experience offers an insight into important considerations for designing assessment frameworks and implementing frameworks in differing contexts. There are lessons which have the potential to improve assessment and reporting practice and quality in not only medical...
... B Thom, B J Canny, M Cowley, P J Wright and I J Clarke Prince Henry's In... more ... B Thom, B J Canny, M Cowley, P J Wright and I J Clarke Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia, 'Department of Physiology, Monash University, Clayton, Victoria 3186, Australia and ^Veterinary Preclinical Sciences, Princes ...
Working memory (WM) is often poorer for a second language (L2). In low noise conditions, people l... more Working memory (WM) is often poorer for a second language (L2). In low noise conditions, people listening to a language other than their first language (L1) may have similar auditory perception skills for that L2 as native listeners, but do worse in high noise conditions, and this has been attributed to the poorer WM for L2. Given that WM is critical for academic success in children and young adults, these speech in noise effects have implications for academic performance where the language of instruction is L2 for a student. We used a well-established Speech-in-Noise task as a verbal WM (vWM) test, and developed a model correlating vWM and measures of English proficiency and/or usage to scholastic outcomes in a multi-faceted assessment medical education program. Significant differences in Speech-Noise Ratio (SNR 50 ) values were observed between medical undergraduates who had learned English before or after five years of age, with the latter group doing worse in the ability to extract whole connected speech in the presence of background multi-talker babble (Student-t tests, p < 0.001). Significant negative correlations were observed between the SNR 50 and seven of the nine variables of English usage, learning styles, stress, and musical abilities in a questionnaire administered to the students previously. The remaining two variables, Perceived Stress Scale (PSS) and the Age of Acquisition of English (AoAoE) were significantly positively correlated with the SNR 50 , showing that those with a poorer capacity to discriminate simple English sentences from noise had learnt English later in life and had higher levels of stress -all characteristics of the international students. Local students exhibited significantly lower SNR 50 scores and were significantly younger when they first learnt English. No significant correlation was detected between the SNR 50 and the students' Visual/Verbal Learning Style (r = −0.023). Standard multiple regression was carried out to assess the relationship between language proficiency and verbal working memory (SNR 50 ) using 5 variables of L2 proficiency, with the results showing that the variance in SNR 50 was significantly predicted by this model (r 2 = 0.335). Hierarchical multiple regression was then used to test the ability of three independent variable measures (SNR 50 , age of acquisition of English and English proficiency) to predict academic performance as the dependent variable in a factor analysis model which predicted significant performance differences in an assessment requiring communications skills (p = 0.008), but How to cite this article Mann et al. , Poorer verbal working memory for a second language selectively impacts academic achievement in university medical students. PeerJ 1:e22;
Six well-trained men (peak pulmonary oxygen uptake = 5.03 +/- 0.11 l/min) were studied during 2 h... more Six well-trained men (peak pulmonary oxygen uptake = 5.03 +/- 0.11 l/min) were studied during 2 h of exercise at 69 +/- 1% peak pulmonary oxygen uptake to examine the effect of carbohydrate (CHO) ingestion on glucose kinetics. Subjects ingested 250 ml of either a 10% glucose solution containing 6-[3H]glucose (CHO) or a sweet placebo every 15 min during exercise. Glucose kinetics were assessed by 6,6-[2H]glucose infusion corrected for gut-derived glucose in CHO. Plasma glucose was higher (P &lt; 0.05) in CHO from 20 min. Total glucose appearance was higher in CHO due to glucose delivery from the gut (68 +/- 7 g), since hepatic glucose production was reduced by 51% (29 +/- 5 vs. 59 +/- 5 g). Glucose uptake was higher in CHO (96 +/- 7 vs. 60 +/- 6 g) with the ingested glucose supplying 67 +/- 4 g and, with the assumption that it was fully oxidized, accounted for 14 +/- 1% of total energy expenditure. In conclusion, CHO ingestion during prolonged exercise results in suppression of hepatic glucose production and increased glucose uptake. These effects appear to be mediated mainly by increased plasma glucose and insulin levels.
AMP-activated protein kinase (AMPK) is a metabolic stress-sensing protein kinase responsible for ... more AMP-activated protein kinase (AMPK) is a metabolic stress-sensing protein kinase responsible for coordinating metabolism and energy demand. In rodents, exercise accelerates fatty acid metabolism, enhances glucose uptake, and stimulates nitric oxide (NO) production in skeletal muscle. AMPK phosphorylates and inhibits acetyl-coenzyme A (CoA) carboxylase (ACC) and enhances GLUT-4 translocation. It has been reported that human skeletal muscle malonyl-CoA levels do not change in response to exercise, suggesting that other mechanisms besides inhibition of ACC may be operating to accelerate fatty acid oxidation. Here, we show that a 30-s bicycle sprint exercise increases the activity of the human skeletal muscle AMPK-alpha1 and -alpha2 isoforms approximately two- to threefold and the phosphorylation of ACC at Ser(79) (AMPK phosphorylation site) approximately 8.5-fold. Under these conditions, there is also an approximately 5.5-fold increase in phosphorylation of neuronal NO synthase-mu (nNOSmu;) at Ser(1451). These observations support the concept that inhibition of ACC is an important component in stimulating fatty acid oxidation in response to exercise and that there is coordinated regulation of nNOSmu to protect the muscle from ischemia/metabolic stress.
The Australian Medical Assessment Collaboration (AMAC) began in 2010. This article charts the dev... more The Australian Medical Assessment Collaboration (AMAC) began in 2010. This article charts the development of the collaboration over its initial years. AMAC was instigated as a way of improving the quality of medical education through the recognition of the need for tools for comparison and evaluation of learning outcomes, acknowledgement of the need for high quality assessment, and to share expertise in these areas. In a climate of increasing regulation and accountability, this collaboration was formed as a means of increasing assessment practices by, with and for medical schools. This article provides an overview of the background issues stimulating the development of AMAC, discussion of the formation of the collaboration and reflection on the lessons learnt through these processes. In a relatively short space of time, AMAC has fostered substantial collaboration among schools; developed an Assessment Framework, items and an online assessment; and provided benchmarking reports to students and schools. The intention here is to provide guidance for others (within the medical education community and those in other disciplines) with similar intentions and aims, by outlining the developmental pathway of the project and the systematic lessons that the collaboration team has learnt in establishing AMAC.
Objectives Generally, in most countries around the world, local medical students outperform, in a... more Objectives Generally, in most countries around the world, local medical students outperform, in an academic sense, international students. In an endeavour to understand if this effect is caused by language proficiency skills, we investigated academic differences between ...
Physiological research / Academia Scientiarum Bohemoslovaca, 2009
The extent to which sex differences in cardiac function may be attributed to the direct myocardia... more The extent to which sex differences in cardiac function may be attributed to the direct myocardial influence of testosterone is unclear. In this study the effects of gonadal testosterone withdrawal (GDX) and replacement (GDX+T) in rats, on cardiomyocyte shortening and intracellular Ca(2+) handling was investigated (0.5 Hz, 25 oC). At all extracellular [Ca(2+)] tested (0.5-2.0 mM), the Ca(2+) transient amplitude was significantly reduced (by approximately 50 %) in myocytes of GDX rats two weeks post-gonadectomy. The time course of Ca(2+) transient decay was significantly prolonged in GDX myocytes (tau, 455+/-80 ms) compared with intact (279+/-23 ms) and GDX+T (277+/-19 ms). Maximum shortening of GDX myocytes was markedly reduced (by more than 60 %) and relaxation significantly delayed (by more than 35 %) compared with intact and GDX+T groups. Thus testosterone replacement completely reversed the cardiomyocyte hypocontractility induced by gonadectomy. These results provide direct evid...
American journal of physiology. Endocrinology and metabolism, 2002
The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protei... more The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protein kinase (AMPK)alpha1 and -alpha2 activity and acetyl-CoA carboxylase (ACCbeta) and neuronal nitric oxide synthase (nNOSmu) phosphorylation was investigated. Seven active healthy individuals cycled for 30 min at a workload requiring 62.8 +/- 1.3% of peak O(2) consumption (VO(2 peak)) with muscle biopsies obtained from the vastus lateralis at rest and at 5 and 30 min of exercise. AMPKalpha1 activity was not altered by exercise; however, AMPKalpha2 activity was significantly (P < 0.05) elevated after 5 min (approximately 2-fold), and further elevated (P < 0.05) after 30 min (approximately 3-fold) of exercise. ACCbeta phosphorylation was increased (P < 0.05) after 5 min (approximately 18-fold compared with rest) and increased (P < 0.05) further after 30 min of exercise (approximately 36-fold compared with rest). Increases in AMPKalpha2 activity were significantly correlated with...
Effect of growth hormone-releasing peptide-2 (GHRP-2) on ovine somatotrophs is abolished by a gro... more Effect of growth hormone-releasing peptide-2 (GHRP-2) on ovine somatotrophs is abolished by a growth hormone-releasing factor (GRF) receptor antagonist, which raises the possibility that GHRP-2 may act on GRF receptors. In the present study, we used rat pituitary GC cells with or without stable transfection of cDNA coding for the human GRF receptor (GC/R+ or GC/R-) to determine whether or not GHRP-2 acts via the GRF receptor. Northern blot analysis indicated that GRF receptor mRNA was undetectable in GC/R-cells, whereas a high level of expression occurred in GC/R+ cells that were transfected by GRF receptor cDNA. In GC/R- cells, incubation with up to 10(-7)M of either hGRF or GHRP-2 did not alter the intracellular cAMP, [Ca2+]i, or GH secretion. In GC/R+ cells, hGRF (10(-11)-10(-7)M) increased cAMP levels in a concentration-dependent manner up to 20-fold. This increase in cAMP levels was blocked by a GRF receptor antagonist, [Ac-Tyr1, D-Arg2]-GRF 1-29, but not by a Ca2+ channel blocker, NiCl2 (0.5 mM). GH secretion and [Ca2+]i were, however, not increased by hGRF. Incubation of the transfected cells with 10(-1)-10(-8)MGH RP-2 did not modify intracellular cAMP levels. This result suggests that GHRP-2 does not act through the GRF receptor.
Skeletal muscle from strength-and endurance-trained individuals represents diverse adaptive state... more Skeletal muscle from strength-and endurance-trained individuals represents diverse adaptive states. In this regard, AMPK-PGC-1α signaling mediates several adaptations to endurance training, while up-regulation of the Akt-TSC2-mTOR pathway may underlie increased protein synthesis after resistance exercise. We determined the effect of prior training history on signaling responses in seven strength-trained and six endurance-trained males who undertook 1 h cycling at 70% VO 2peak or eight sets of five maximal repetitions of isokinetic leg extensions. Muscle biopsies were taken at rest, immediately and 3 h postexercise. AMPK phosphorylation increased after cycling in strength-trained (54%; P<0.05) but not endurance-trained subjects. Conversely, AMPK was elevated after resistance exercise in endurance-(114%; P<0.05), but not strengthtrained subjects. Akt phosphorylation increased in endurance-(50%; P<0.05), but not strengthtrained subjects after cycling but was unchanged in either group after resistance exercise. TSC2 phosphorylation was decreased (47%; P<0.05) in endurance-trained subjects following resistance exercise, but cycling had little effect on the phosphorylation state of this protein in either group. p70S6K phosphorylation increased in endurance-(118%; P<0.05), but not strength-trained subjects after resistance exercise, but was similar to rest in both groups after cycling. Similarly, phosphorylation of S6 protein, a substrate for p70 S6K, was increased immediately following resistance exercise in endurance-(129%; P<0.05), but not strength-trained subjects. In conclusion, a degree of "response plasticity" is conserved at opposite ends of the endurancehypertrophic adaptation continuum. Moreover, prior training attenuates the exercise specific signaling responses involved in single mode adaptations to training.
These experiments are concerned with the ability of human subjects to match isometric torque in t... more These experiments are concerned with the ability of human subjects to match isometric torque in their elbow flexor muscles when biceps of one arm is made sore. Pain was induced by injection of hypertonic saline. Subjects were asked to generate a level of torque, 30% of maximum, with one arm, the reference arm. To achieve the required torque, subjects were given visual feedback. Subjects were then asked to match this torque with their other arm, the indicator arm. In control measurements, subjects were consistent in their matching ability and often were quite accurate. However, when biceps of one arm was made sore, subjects consistently and significantly underestimated the level of torque being generated by the sore arm. Painful heat applied to the skin over biceps produced a similar pattern of errors. Heating skin remote from elbow flexors had no significant effect. One interpretation of these findings is that the nociceptive input from the sore region of skin or muscle leads to reduced excitability of the motor cortex. That, in turn, disturbs the relationship between the centrally generated effort and motor output, leading to matching errors.
Despite evidence that +/-3,4-methylenedioxymethamphetamine (MDMA; &amp;amp;#39;ecstasy&am... more Despite evidence that +/-3,4-methylenedioxymethamphetamine (MDMA; &amp;amp;#39;ecstasy&amp;amp;#39;) causes persistent alterations to the serotonergic system of animals, evidence for long-term neurological effects of ecstasy/MDMA in humans remains equivocal. The current study assessed serotonin functioning of nine male and 11 female recreational ecstasy polydrug users by measuring neuroendocrine (prolactin, cortisol) responses to pharmacological challenge with the selective serotonin reuptake inhibitor citalopram, compared with nine male and five female cannabis polydrug users and 11 male and 11 female non-drug using controls. A single-blind, randomised, placebo-controlled design was used. Subjective responses, other substance use, mood, personality traits and demographic variables were measured to control for potentially confounding variables. There were no significant differences between ecstasy polydrug users, cannabis polydrug users and non-drug using controls in neuroendocrine or subjective responses to serotonergic challenge, and there were no sex by drug group interactions. There was no relationship between extent of ecstasy use and neuroendocrine functioning, alone or in combination with potential confounding variables. Subjective responses to the pharmacological challenge (nausea, tremor, dry mouth), novelty seeking and lifetime dose of alcohol were the only variables that contributed to one or more of the neuroendocrine outcome variables. These data do not support the premise that recreational ecstasy/MDMA use results in measurable impairment of serotonergic control of endocrine activity.
The two fundamental parameters of corticotropin (ACTH) secretion are the number of secreting cort... more The two fundamental parameters of corticotropin (ACTH) secretion are the number of secreting corticotropes and the amount of ACTH secreted by each cell. We have measured these parameters in rat corticotropes in response to increasing concentrations of corticotropin-releasing factor (CRF) or arginine vasopressin (AVP). Increasing concentrations of AVP stimulated more corticotropes to secrete, while the amount of ACTH each cell secreted remained relatively fixed (nongraded secretory response). Conversely, increasing concentrations of CRF stimulated more ACTH secretion per cell (graded secretory response), while the number of secretory cells remained relatively constant. When viewed from the perspective of a single corticotrope, it was clear that CRF and AVP induced completely distinct specific responses. We have previously shown, and provide further evidence here, that secretory responses to CRF or AVP occur in the same cell. It is therefore apparent that a single corticotrope is able to generate either a graded, or a nongraded secretory response. We have also considered the potential intracellular changes that must direct graded or nongraded secretion. It is generally accepted that CRF stimulates activation of adenylate cyclase, whereas AVP activates phosphoinositidase in pituitary corticotropes. Our findings, and others surveyed here, suggest that the activation of adenylate cyclase results in graded secretion, while the activation of phosphoinositidase induces the nongraded secretion. Graded or nongraded secretion may therefore be linked to specific second messengers. It is hypothesized that the inositol 1,4,S-trisphosphate-mediated release of an intracellular Ca2+ store constitutes a mechanism whereby phosphoinositidase-coupled hormones set in motion the nongraded secretory response. These findings suggest novel functions for individual second messengers.
Local communication among cells of the anterior pituitary appears to play an important role in th... more Local communication among cells of the anterior pituitary appears to play an important role in the regulation of ACTH secretion. Dissociated pituitary cells were plated as a monolayer at decreasing concentrations of cells (increasing the distance between cells and, thus, decreasing their potential interactions), and ACTH secretion was measured from individual corticotropes using a specific reverse hemolytic plaque assay. There was a critical intercell distance above which significant changes in the number of CRF-responsive corticotropes were observed. Provided that this critical distance was not exceeded the number of secretory corticotropes in response to CRF (10 nM) was relatively constant, thereby defining a fraction of corticotropes that was robustly CRF responsive. In contrast, when this critical distance between cells was exceeded, the number of CRF-responsive corticotropes progressively increased to almost double their original number, thereby defining a second fraction of CRF-responsive corticotropes that was previously repressed. These observations suggest the presence of a paracrine factor that profoundly inhibits CRF-stimulated ACTH secretion from a repressed fraction of corticotropes. Further independent studies confirmed and extended these observations. We identified the cellular source of the inhibitory factor as the robustly CRF-responsive fraction of corticotropes. Pituitary cells were identified by reverse hemolytic plaque assay and then destroyed using a laser photoablation procedure that did not compromise the remaining cells. The pituitary cells were separated by a distance at which the inhibitory factor was fully effective. Destruction of the cellular source of the paracrine inhibition would, therefore, allow secretion from the previously repressed fraction of corticotropes. Accordingly, when robustly CRF-responsive corticotropes were destroyed, a significant number of previously repressed corticotropes appeared in a second assay. Destruction of somatotropes or a cell adjacent to a robustly CRF-responsive corticotrope did not alter the number of CRF-stimulated corticotropes among the remaining cells. We conclude that a paracrine factor liberated by the robustly CRF-responsive corticotropes inhibits ACTH secretion from the repressed fraction of corticotropes. The robustly CRF-responsive corticotropes appear unresponsive to the effects of the factor, and the repressed corticotropes are unlikely to secrete it. A role of this paracrine communication is to hold corticotropes in reserve and, therefore, prevent the severe depletion of hormone. This form of paracrine communication may be a specialized adaption among cells where the physiological setting demands robust secretory responses to multiple stimuli. The experimental paradigms developed here may be extremely useful for 1) screening potential paracrine factors and 2) determining whether the secretion of the paracrine factor is regulated by adrenal or hypothalamic hormones.
An assessment framework provides a structured conceptual map of the learning outcomes of a progra... more An assessment framework provides a structured conceptual map of the learning outcomes of a programme of study along with details of how achievement of the outcomes can be measured. The rationale for using frameworks to underpin the targeting of essential content components is especially relevant for the medical education community. Frameworks have the capacity to improve validity and reliability in assessment, allowing test developers to more easily create robust assessment instruments. The framework used by the Australian Medical Assessment Collaboration (AMAC) is an interesting and relevant case study for the international community as it draws and builds on established processes in higher education assessment. The AMAC experience offers an insight into important considerations for designing assessment frameworks and implementing frameworks in differing contexts. There are lessons which have the potential to improve assessment and reporting practice and quality in not only medical...
... B Thom, B J Canny, M Cowley, P J Wright and I J Clarke Prince Henry&amp;amp;amp;#x27;s In... more ... B Thom, B J Canny, M Cowley, P J Wright and I J Clarke Prince Henry&amp;amp;amp;#x27;s Institute of Medical Research, PO Box 5152, Clayton, Victoria 3168, Australia, &amp;amp;amp;#x27;Department of Physiology, Monash University, Clayton, Victoria 3186, Australia and ^Veterinary Preclinical Sciences, Princes ...
Working memory (WM) is often poorer for a second language (L2). In low noise conditions, people l... more Working memory (WM) is often poorer for a second language (L2). In low noise conditions, people listening to a language other than their first language (L1) may have similar auditory perception skills for that L2 as native listeners, but do worse in high noise conditions, and this has been attributed to the poorer WM for L2. Given that WM is critical for academic success in children and young adults, these speech in noise effects have implications for academic performance where the language of instruction is L2 for a student. We used a well-established Speech-in-Noise task as a verbal WM (vWM) test, and developed a model correlating vWM and measures of English proficiency and/or usage to scholastic outcomes in a multi-faceted assessment medical education program. Significant differences in Speech-Noise Ratio (SNR 50 ) values were observed between medical undergraduates who had learned English before or after five years of age, with the latter group doing worse in the ability to extract whole connected speech in the presence of background multi-talker babble (Student-t tests, p < 0.001). Significant negative correlations were observed between the SNR 50 and seven of the nine variables of English usage, learning styles, stress, and musical abilities in a questionnaire administered to the students previously. The remaining two variables, Perceived Stress Scale (PSS) and the Age of Acquisition of English (AoAoE) were significantly positively correlated with the SNR 50 , showing that those with a poorer capacity to discriminate simple English sentences from noise had learnt English later in life and had higher levels of stress -all characteristics of the international students. Local students exhibited significantly lower SNR 50 scores and were significantly younger when they first learnt English. No significant correlation was detected between the SNR 50 and the students' Visual/Verbal Learning Style (r = −0.023). Standard multiple regression was carried out to assess the relationship between language proficiency and verbal working memory (SNR 50 ) using 5 variables of L2 proficiency, with the results showing that the variance in SNR 50 was significantly predicted by this model (r 2 = 0.335). Hierarchical multiple regression was then used to test the ability of three independent variable measures (SNR 50 , age of acquisition of English and English proficiency) to predict academic performance as the dependent variable in a factor analysis model which predicted significant performance differences in an assessment requiring communications skills (p = 0.008), but How to cite this article Mann et al. , Poorer verbal working memory for a second language selectively impacts academic achievement in university medical students. PeerJ 1:e22;
Six well-trained men (peak pulmonary oxygen uptake = 5.03 +/- 0.11 l/min) were studied during 2 h... more Six well-trained men (peak pulmonary oxygen uptake = 5.03 +/- 0.11 l/min) were studied during 2 h of exercise at 69 +/- 1% peak pulmonary oxygen uptake to examine the effect of carbohydrate (CHO) ingestion on glucose kinetics. Subjects ingested 250 ml of either a 10% glucose solution containing 6-[3H]glucose (CHO) or a sweet placebo every 15 min during exercise. Glucose kinetics were assessed by 6,6-[2H]glucose infusion corrected for gut-derived glucose in CHO. Plasma glucose was higher (P &lt; 0.05) in CHO from 20 min. Total glucose appearance was higher in CHO due to glucose delivery from the gut (68 +/- 7 g), since hepatic glucose production was reduced by 51% (29 +/- 5 vs. 59 +/- 5 g). Glucose uptake was higher in CHO (96 +/- 7 vs. 60 +/- 6 g) with the ingested glucose supplying 67 +/- 4 g and, with the assumption that it was fully oxidized, accounted for 14 +/- 1% of total energy expenditure. In conclusion, CHO ingestion during prolonged exercise results in suppression of hepatic glucose production and increased glucose uptake. These effects appear to be mediated mainly by increased plasma glucose and insulin levels.
AMP-activated protein kinase (AMPK) is a metabolic stress-sensing protein kinase responsible for ... more AMP-activated protein kinase (AMPK) is a metabolic stress-sensing protein kinase responsible for coordinating metabolism and energy demand. In rodents, exercise accelerates fatty acid metabolism, enhances glucose uptake, and stimulates nitric oxide (NO) production in skeletal muscle. AMPK phosphorylates and inhibits acetyl-coenzyme A (CoA) carboxylase (ACC) and enhances GLUT-4 translocation. It has been reported that human skeletal muscle malonyl-CoA levels do not change in response to exercise, suggesting that other mechanisms besides inhibition of ACC may be operating to accelerate fatty acid oxidation. Here, we show that a 30-s bicycle sprint exercise increases the activity of the human skeletal muscle AMPK-alpha1 and -alpha2 isoforms approximately two- to threefold and the phosphorylation of ACC at Ser(79) (AMPK phosphorylation site) approximately 8.5-fold. Under these conditions, there is also an approximately 5.5-fold increase in phosphorylation of neuronal NO synthase-mu (nNOSmu;) at Ser(1451). These observations support the concept that inhibition of ACC is an important component in stimulating fatty acid oxidation in response to exercise and that there is coordinated regulation of nNOSmu to protect the muscle from ischemia/metabolic stress.
The Australian Medical Assessment Collaboration (AMAC) began in 2010. This article charts the dev... more The Australian Medical Assessment Collaboration (AMAC) began in 2010. This article charts the development of the collaboration over its initial years. AMAC was instigated as a way of improving the quality of medical education through the recognition of the need for tools for comparison and evaluation of learning outcomes, acknowledgement of the need for high quality assessment, and to share expertise in these areas. In a climate of increasing regulation and accountability, this collaboration was formed as a means of increasing assessment practices by, with and for medical schools. This article provides an overview of the background issues stimulating the development of AMAC, discussion of the formation of the collaboration and reflection on the lessons learnt through these processes. In a relatively short space of time, AMAC has fostered substantial collaboration among schools; developed an Assessment Framework, items and an online assessment; and provided benchmarking reports to students and schools. The intention here is to provide guidance for others (within the medical education community and those in other disciplines) with similar intentions and aims, by outlining the developmental pathway of the project and the systematic lessons that the collaboration team has learnt in establishing AMAC.
Objectives Generally, in most countries around the world, local medical students outperform, in a... more Objectives Generally, in most countries around the world, local medical students outperform, in an academic sense, international students. In an endeavour to understand if this effect is caused by language proficiency skills, we investigated academic differences between ...
Physiological research / Academia Scientiarum Bohemoslovaca, 2009
The extent to which sex differences in cardiac function may be attributed to the direct myocardia... more The extent to which sex differences in cardiac function may be attributed to the direct myocardial influence of testosterone is unclear. In this study the effects of gonadal testosterone withdrawal (GDX) and replacement (GDX+T) in rats, on cardiomyocyte shortening and intracellular Ca(2+) handling was investigated (0.5 Hz, 25 oC). At all extracellular [Ca(2+)] tested (0.5-2.0 mM), the Ca(2+) transient amplitude was significantly reduced (by approximately 50 %) in myocytes of GDX rats two weeks post-gonadectomy. The time course of Ca(2+) transient decay was significantly prolonged in GDX myocytes (tau, 455+/-80 ms) compared with intact (279+/-23 ms) and GDX+T (277+/-19 ms). Maximum shortening of GDX myocytes was markedly reduced (by more than 60 %) and relaxation significantly delayed (by more than 35 %) compared with intact and GDX+T groups. Thus testosterone replacement completely reversed the cardiomyocyte hypocontractility induced by gonadectomy. These results provide direct evid...
American journal of physiology. Endocrinology and metabolism, 2002
The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protei... more The effect of prolonged moderate-intensity exercise on human skeletal muscle AMP-activated protein kinase (AMPK)alpha1 and -alpha2 activity and acetyl-CoA carboxylase (ACCbeta) and neuronal nitric oxide synthase (nNOSmu) phosphorylation was investigated. Seven active healthy individuals cycled for 30 min at a workload requiring 62.8 +/- 1.3% of peak O(2) consumption (VO(2 peak)) with muscle biopsies obtained from the vastus lateralis at rest and at 5 and 30 min of exercise. AMPKalpha1 activity was not altered by exercise; however, AMPKalpha2 activity was significantly (P < 0.05) elevated after 5 min (approximately 2-fold), and further elevated (P < 0.05) after 30 min (approximately 3-fold) of exercise. ACCbeta phosphorylation was increased (P < 0.05) after 5 min (approximately 18-fold compared with rest) and increased (P < 0.05) further after 30 min of exercise (approximately 36-fold compared with rest). Increases in AMPKalpha2 activity were significantly correlated with...
Effect of growth hormone-releasing peptide-2 (GHRP-2) on ovine somatotrophs is abolished by a gro... more Effect of growth hormone-releasing peptide-2 (GHRP-2) on ovine somatotrophs is abolished by a growth hormone-releasing factor (GRF) receptor antagonist, which raises the possibility that GHRP-2 may act on GRF receptors. In the present study, we used rat pituitary GC cells with or without stable transfection of cDNA coding for the human GRF receptor (GC/R+ or GC/R-) to determine whether or not GHRP-2 acts via the GRF receptor. Northern blot analysis indicated that GRF receptor mRNA was undetectable in GC/R-cells, whereas a high level of expression occurred in GC/R+ cells that were transfected by GRF receptor cDNA. In GC/R- cells, incubation with up to 10(-7)M of either hGRF or GHRP-2 did not alter the intracellular cAMP, [Ca2+]i, or GH secretion. In GC/R+ cells, hGRF (10(-11)-10(-7)M) increased cAMP levels in a concentration-dependent manner up to 20-fold. This increase in cAMP levels was blocked by a GRF receptor antagonist, [Ac-Tyr1, D-Arg2]-GRF 1-29, but not by a Ca2+ channel blocker, NiCl2 (0.5 mM). GH secretion and [Ca2+]i were, however, not increased by hGRF. Incubation of the transfected cells with 10(-1)-10(-8)MGH RP-2 did not modify intracellular cAMP levels. This result suggests that GHRP-2 does not act through the GRF receptor.
Skeletal muscle from strength-and endurance-trained individuals represents diverse adaptive state... more Skeletal muscle from strength-and endurance-trained individuals represents diverse adaptive states. In this regard, AMPK-PGC-1α signaling mediates several adaptations to endurance training, while up-regulation of the Akt-TSC2-mTOR pathway may underlie increased protein synthesis after resistance exercise. We determined the effect of prior training history on signaling responses in seven strength-trained and six endurance-trained males who undertook 1 h cycling at 70% VO 2peak or eight sets of five maximal repetitions of isokinetic leg extensions. Muscle biopsies were taken at rest, immediately and 3 h postexercise. AMPK phosphorylation increased after cycling in strength-trained (54%; P<0.05) but not endurance-trained subjects. Conversely, AMPK was elevated after resistance exercise in endurance-(114%; P<0.05), but not strengthtrained subjects. Akt phosphorylation increased in endurance-(50%; P<0.05), but not strengthtrained subjects after cycling but was unchanged in either group after resistance exercise. TSC2 phosphorylation was decreased (47%; P<0.05) in endurance-trained subjects following resistance exercise, but cycling had little effect on the phosphorylation state of this protein in either group. p70S6K phosphorylation increased in endurance-(118%; P<0.05), but not strength-trained subjects after resistance exercise, but was similar to rest in both groups after cycling. Similarly, phosphorylation of S6 protein, a substrate for p70 S6K, was increased immediately following resistance exercise in endurance-(129%; P<0.05), but not strength-trained subjects. In conclusion, a degree of "response plasticity" is conserved at opposite ends of the endurancehypertrophic adaptation continuum. Moreover, prior training attenuates the exercise specific signaling responses involved in single mode adaptations to training.
These experiments are concerned with the ability of human subjects to match isometric torque in t... more These experiments are concerned with the ability of human subjects to match isometric torque in their elbow flexor muscles when biceps of one arm is made sore. Pain was induced by injection of hypertonic saline. Subjects were asked to generate a level of torque, 30% of maximum, with one arm, the reference arm. To achieve the required torque, subjects were given visual feedback. Subjects were then asked to match this torque with their other arm, the indicator arm. In control measurements, subjects were consistent in their matching ability and often were quite accurate. However, when biceps of one arm was made sore, subjects consistently and significantly underestimated the level of torque being generated by the sore arm. Painful heat applied to the skin over biceps produced a similar pattern of errors. Heating skin remote from elbow flexors had no significant effect. One interpretation of these findings is that the nociceptive input from the sore region of skin or muscle leads to reduced excitability of the motor cortex. That, in turn, disturbs the relationship between the centrally generated effort and motor output, leading to matching errors.
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Papers by Benedict Canny